Protein Kinases and their Modulation in the Central Nervous System

Protein kinases (PKs) mediate neuronal morphology, differentiation, survival, repair, and plasticity in central nervous system (CNS). In this review, the structure and function of PKs involved in CNS function, various neurological disorders, learning process, and memory are discussed. Certain types of PKs and their ligands have been implicated in memory and learning, axon guidance, the formation of neural projections, axon fasciculation, cell migration, and neurotrophin signaling. Many of these functions are regulated via the action of protein tyrosine kinases (PTKs) and their ligands, such as epidermal growth factor (EGF) receptor, Janus kinase-signal transducer and activator of transcription (JAK/STAT), Fyn-tyrosine kinase, Eph receptors, and neurotrophins (NTs) [e.g., brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)]. Serine/threonine kinases, such as activins, bone morphogenic proteins (BMPs), mitogen-activated protein (MAP) kinases (e.g., p44/42 MAPK, c-Jun N-terminal kinase, p38 MAPKs), and protein kinases A (PKA) and C (PKC) and their function in the CNS are also discussed. The role of protein kinase inhibitors (PKIs), isolated from microbial, botanical sources or synthesized by conventional approaches, in determining CNS signaling cascades and function, and the treatment of neurological disorders is reviewed.